Implants and methods for manufacturing same

ABSTRACT

Implantable prosthesis, components of prosthesis, and methods of making same are provided. The methods generally include the steps of providing an implant shell, applying a curable fluid composition to the shell to form a coating thereon and applying a particulate component to the composition. The composition is a mixture, for example, an emulsion, containing a silicone-based elastomer dispersion and droplets of a suspended leachable agent. After the elastomer is stabilized and cured, the particulate component and leachable agent are removed, resulting in an implantable member having a porous, open-cell surface texture designed to be effective in reducing incidence of capsular formation or contraction.

RELATED APPLICATION

This application is a continuation of U.S. patent application Ser. No.13/942,104, filed October Jul. 15, 2013, now U.S. Pat. No. 8,951,596,which is a continuation of U.S. patent application Ser. No. 12/897,498,filed Oct. 4, 2010, now abandoned, which claims priority to U.S.Provisional Patent Application No. 61/252,330, filed on Oct. 16, 2009,the entire disclosures of each of which are incorporated herein by thisspecific reference.

BACKGROUND

The present invention generally relates to soft tissue implants and morespecifically relates to soft tissue implants designed to enhancefixation in the body and/or alter or reduce capsular formation.

Soft tissue implants, particularly mammary prostheses, are plagued byproblems of capsular formation and contracture. Soon after an implant isplaced into the body, an inflammatory response begins to deposit afibrous capsule around the implant. In most cases, particularly forrelatively large and smooth implants, the capsule is comprised of highlyorganized or aligned collagen fibers. As the capsule matures, certainevents may trigger the differentiation of fibroblasts to a contractilephenotype (myofibroblasts). In this or similar scenarios, and if thecollagen fibers are aligned, capsular contracture may ensue.

Capsular contracture can be debilitating to the patient because ofdiscomfort or even pain caused thereby, can diminish the efficacy of theaesthetic results in both the look and feel of the implant, and cansometimes damage the implant itself. Problems with capsular formationand contracture occur in many implant types such as pacemakers, duramatter substitutes, implantable cardiac defibrillators, pacemaker leads,hernia repair meshes as well as breast and other esthetic implants.

It has been established in the literature that surface texturing ofimplants often helps to reduce the incidence of capsular contracturewhen compared to smooth surface implants. Furthermore there isincreasing evidence regarding the ability of foam covered implants, forexample, polyurethane foam coated implants, to reduce contracture rates.However, polyurethane foam coatings are biodegradable and lose theirefficacy once the polyurethane degrades. Further, it can be appreciatedthat degradation of polyurethane foam into the body is undesirable andpotentially unhealthy.

The present invention addresses at least some of these drawbacks ofconventional implants.

SUMMARY OF THE INVENTION

The present invention provides implantable members and methods formanufacturing implantable members, for example, prostheses, for example,mammary prostheses, as well as components of prostheses, for example,elastomeric shells, which serve as components of mammary prostheses. Theinvention further provides coverings, for example, laminates forapplying to surfaces of implantable devices. The implantable membershave surfaces which may enhance fixation and/or alter or reduce capsularformation. In one aspect of the invention, the textured surfaces aredefined by a network of interconnected pores and channels whichencourages tissue ingrowth and discourages organization of the collagencapsule. Generally, the pores have, on average, more than twointerconnections assuming that the average number of interconnectionsper pore does not vary significantly.

The method generally comprises the steps of providing an implantablemember, for example an implant shell, for example, a conventional smoothsilicone-based implant shell, and applying a curable fluid compositionto the shell to form a coating thereon. In one embodiment, thecomposition comprises a silicone-based mixture including a solvent, anda pore-forming material, for example, a leachable agent, dispersedtherein. The composition is allowed to stabilize on the shell, forexample, by allowing some of the solvent to evaporate out of thecomposition or allowing a chemical reaction to occur inducingprecipitation of the soluble components. Alternatively, stabilizationcan be achieved during crosslinking of polymerization of the silicone,precipitation of the silicone or pore-forming material of a combinationof the above alone or in conjunction with solvent evaporation.

Next, a particulate component, hereinafter sometimes simply referred toas “particles” or a “particle coating”, is applied to the compositioncoating while the composition coating is less than entirely cured, or atleast has a stickiness or tackiness capable of retaining the particulatecoating.

In some embodiments, the steps of applying a curable fluid compositionand applying a particle coating are then repeated, for example, one ormore times, for example, three, five or even up to 20 times, until afinal coating is applied. The final coating may be a particle coating ora composition coating.

After the final coating of particles or fluid composition is applied tothe shell, the coated shell is then subjected to suitable curingconditions to solidify the composition with the particles embeddedtherein.

In one embodiment, the particulate coating itself is used to stabilizethe coating composition, for example, by absorbing some or all of thesolvent, increasing the rate of polymerization of crosslinking of thesilicone, promoting precipitation of the silicone or porogen, or acombination of one or more of the above.

Once solidified, the leachable agent contained in the composition andthe particles embedded therein are then removed from the coating therebyrevealing a network of interconnected pores (the structure may includeboth relatively large pores and relatively smaller pores, for example,micropores) within the cured elastomer. The surface topography createdby the processes described herein, when used as a part of an implant atthe tissue/implant interface, may be highly effective in alteringcapsular formation so as to achieve a more preferred morphology, or inreducing or preventing capsular contracture, relative to conventionalsurface topographies.

Removal of the particles and leachable agent may be accomplished by anysuitable means effective to remove these materials from the surroundingelastomer “matrix”, and create the desirable surface topography.

For example, the particles and/or leachable agent(s) may be extracted byexposing the coating to one or more suitable mediums capable ofdissolving, extracting or otherwise removing the particles and/orleachable agent while leaving the cured elastomer matrix generallyintact.

Generally, the particles, which are typically larger in size than thedispersed leachable agent, serve to create cavities or pores in thecured elastomer while the dispersed leachable agent serves to createmicrocavities or micropores which serve as interconnections between thepores. This network of interconnected pores and micropores facilitatestissue ingrowth, encourages better fixation of the implant in thepatient, and discourages organization of the fibrous capsule, which mayhelp reduce or prevent capsule formation and contraction.

BRIEF DESCRIPTION OF THE DRAWINGS

The present invention may be more clearly understood and the aspects andadvantages thereof more clearly appreciated with reference to thefollowing detailed description and accompanying drawings of which:

FIGS. 1A-1C represents suitable process steps in a method formanufacturing an elastomeric shell in accordance with an embodiment ofthe invention;

FIGS. 2-6 are cross-sectional views of components of the shell duringvarious steps of the process for making the shell shown in FIGS. 1A-1C.

FIG. 7 is a simplified flow chart showing steps in a method formanufacturing an implant shell in accordance with an embodiment of theinvention.

DETAILED DESCRIPTION

Accordingly, implantable composite members and methods for manufacturingsuch implantable composite members are provided.

In one aspect of the invention, the present invention provides animplantable composite member, hereinafter, typically referred to as an“implant”, having a surface that renders the implant effective inreducing the occurrence or severity of capsule formation when theimplant is placed in the body. In a specific exemplary embodiment thatwill now be described, the implant is a fillable mammary prosthesisuseful in breast reconstruction or breast augmentation. It should beappreciated, however, that the present invention is not limited tomammary prostheses, but is useful in many situations in which an implantis intended to be permanently or temporarily placed in the body andwhich capsule formation or contraction is to be avoided or impaired.

First, in a method of the invention, an implant member is provided. Theimplant member may be a fillable, elastomeric implant shell having aconfiguration of a breast prosthesis. Such shells are intended to befilled, typically, with saline or silicone gel before or afterimplantation in the breast.

Generally, manufacture of such shells is commonly accomplished byapplying a liquid dispersion, for example, a silicone elastomerdispersion, to a mandrel having a desired form. The dispersion generallycontains a silicone elastomer and a solvent. The silicone elastomer maybe polydimethylsiloxane, polydiphenyl-siloxane or some combination ofthese two materials. Typical solvents include xylene, trichloromethane,heptane, hexane, and toluene.

The silicone dispersion forms an elastomeric coating on the mandrel. Thecoating is cured and the solvent evaporates therefrom. This proceduremay be repeated a number of times in order to obtain an implant shellhaving a desired thickness. This shell may be used as base component formany of the implants of the present invention.

In accordance with one aspect of the invention, an implantable memberhaving a desired surface topography is provided. The method comprisesthe steps of applying a curable fluid composition to a substrate, forexample, a surface of an implant shell described above, applying aparticulate material to the composition, and in some instances,repeating these steps to achieve layers, for example, alternating layersof composition and particulates. The composition includes a leachablecomponent to be described elsewhere herein. The composition layers areallowed to stabilize between subsequent applications.

Once the layering steps are completed, the composition is subject toconditions to allow it to at least partially cure. Curing process stepswill depend on the materials used. One or more process steps areperformed to remove the particles of the particle layer(s) and theleachable component from the elastomer.

The resulting implant has an external surface at least a portion ofwhich is an open-cell porous structure having a topography or porositythat affects capsule formation and/or adhesion of the implant whenimplanted in a patient.

The curable fluid composition may be in the form of an emulsion,dispersion, solution, suspension or mixture containing an elastomercomponent, a solvent component and a leachable component.

The elastomer component may be an uncured silicone polymer, for example,a silicone elastomer. For example, in some embodiments, the elastomercomponent is a room temperature vulcanizing (RTV) silicone elastomer.The elastomer component may be polydimethyl siloxane, polydiphenylsiloxane or a combination of these two. Possible silicone elastomersystems useful in the present invention include, but are not limited to,oxime, platinum or tin catalyst based systems. Alternatively, theelastomer component may be a non-silicone based material.

The solvent component may be any suitable solvent or solvent system,appropriate to the elastomer. Representative examples of solventsinclude chloroform, acetone, water (buffered saline), dimethyl sulfoxide(DMSO), propylene glycol methyl ether (PM), isopropyl alcohol (IPA),n-propyl alcohol, methanol, ethanol, tetrahydrofuran (THF),dimethylformamide (DMF), dimethyl acetamide (DMAC), N-Methylpyrrolidone(NMP), benzene, toluene, xylene, hexane, cyclohexane, heptane, octane,pentane, nonane, decane, decalin, ethyl acetate, butyl acetate, isobutylacetate, isopropyl acetate, butanol, diacetone alcohol, benzyl alcohol,2-butanone, cyclohexanone, dioxane, methylene chloride, carbontetrachloride, tetrachloroethylene, tetrachloro ethane, chlorobenzene,1,1,1-trichloroethane, formamide, hexafluoroisopropanol,1,1,1-trifluoroethanol, and hexamethyl phosphoramide and combinationsthereof. In one embodiment, the solvent is selected from the group ofsolvents consisting of xylene, pentane, hexane, heptane,dichloromethane, trichloromethane, toluene, dimethyl sulfoxide, dioxane,NMP, DMAC, and combinations thereof. The solvent component may compriseone or more different solvents. For example, the solvent component maycomprise between one and twenty different solvents. Generally, thesolvent may comprise any suitable protic or aprotic solvent, mixture orsolution thereof.

The leachable component is a leachable material/agent in the form of anysuitable solid particulates, semi-solids, composites, gels, for example,hydrogels, liquid droplets, etc. The leachable agent may comprise anysuitable polymer, ceramic, metal, composite or combination thereof thatcan be dissolved or otherwise removed by suitable means from the curedformulation. In some embodiments, the composition comprises one or moredifferent leachable agents. For example, the composition may comprisebetween one and twenty different types of leachable agents.

The elastomer component can be present in the composition in a range ofabout 1% to about 99% of volume as part of the total dissolved solidsand the leachable agent can be in the range of about 1% to about 99% ofvolume as part of the total dissolved solids. In a specific embodimentof the invention, the composition includes up to 96% leachable phase. Insome embodiments, the elastomer component is present in the compositionin a range of about 5% to about 80% and the leachable agent is presentin the composition in a range of about 20% to about 95% of totaldissolved solids. Generally, the total dissolved solids in thecomposition can range from about 1′)/0 to about 50% by weight insolution.

The ratio of leachable phase to matrix phase in the compositiongenerally affects the porosity of the final cured composition. Forexample, a greater percentage of leachable component in the compositionwill produce a composition layer having greater interconnections betweenpores.

In an exemplary embodiment, the curable fluid composition is in the formof an emulsion, and the leachable agent is present in a concentration ofup to about 50% concentration by volume of the emulsion. In someembodiments, the composition comprises a microphase separationcontaining an elastomer matrix phase and droplets of leachable materialin suspended phase, the droplets being about 0.01 μm to about 10,000 μmin diameter, for example, about 1 μm to about 5,000 μm in diameter, forexample, about 50 μm to about 400 μm in diameter. After the leachableagent has been leached from the elastomer, voids left behind by theleachable agent will serve as interconnections between voids left by theremoved particles.

The leachable agent may be, for example, any material that can bedispersed through the elastomer dispersion (elastomer component/solventsystem) and can be removed therefrom once the elastomer component iscured. The leachable agent may be an agent that can be removed from thecured elastomer, for example, by leaching, evaporation, sublimation,dissolution, etc. In an exemplary embodiment, the leachable agent is awater soluble material dispersed throughout the elastomer dispersion.

Typical leachable agent in accordance with the invention may comprise,for example, polyethylene glycol (PEG) (also known as polyoxyethylene),polyalkylene oxides including polyethylene oxide and polyethyleneoxide/polypropylene oxide copolymers (also known as poloxamers),polyhydroxyethylmethacrylate, polyvinylpyrrolidone, polyacrylamide andits copolymers, polylactides, polyglycolides, polyanhydrides,polyorthoesters and their copolymers, proteins including albumin,peptides, liposomes, cationic lipids, ionic or nonionic detergents,salts including potassium chloride, sodium chloride and calciumchloride; sugars including galactose, glucose and sucrose;polysaccharides including soluble celluloses, heparin, cyclodextrins anddextran; and any combination thereof.

In some embodiments, the leachable agent is an agent selected from thegroup of agents consisting of polyvinyl alcohol, polyethylene glycol,polyacrylic acid, polymethacrylate, poly-lactide, polyglycolide,polycaprolatone, polydioxanone; and derivatives, blends, copolymers,terpolymers, and combinations thereof.

In some embodiments, the leachable agent is in the form of droplets ofleachable material having diameters in a range of between about 0.01micron to about 10,000 microns. For example, the leachable agent may bein the form of droplets having diameters in a range of between about 1micron to about 5,000 microns, for example, in a range of between about50 microns to about 400 microns.

The particulates of the particle layer comprise any suitable particleswhich may be removed from the cured elastomer, leaving cavities wherethe particles had been.

For example, the particles may comprise particles that can be removedfrom the elastomer by at least one of mechanical abrasion, leaching,evaporation, sublimation, dissolution etc.

In an exemplary embodiment, the particles are a solid, water solublematerial. For example, the particles may be material selected from thegroup of materials consisting of sodium chloride, barium sulfate,potassium nitrate and sodium carbonate.

In addition, the particles may have dimensions and shapes as desired tobring about a resulting topography. For example, the particles may besubstantially round or spherical, multifaceted, angular, or cubic or acombination thereof. The particles may have an average particle size ina range of between about 0.01 micron to about 10,000 microns, forexample, in a range of between about 10 microns to about 6,000 microns,for example, in a range of between about 100 microns to about 900microns.

In some embodiments, the size of the particles is approximatelyproportional to the thickness of the composition coating on which theyare deposited, or the thickness of adjacent interconnecting compositioncoatings in a multilayered embodiment. For example, particles with anaverage size of about 500 micron could be used in conjunction with acomposition layer having a thickness of about 100 microns to about 500microns. For particles with an average size of about 300 microns, acomposition layer of about 50 microns to about 400 microns could beused.

FIGS. 1A-1C illustrate an exemplary process for making an implant inaccordance with an embodiment of the invention. Step one is illustratedin 1A. In FIG. 1A, a flexible, elastomeric implantable member 12 isdepicted. The partial cross sectional view 11 of the elastomeric implantmember 12 is shown in FIG. 1A as well as FIG. 2. The implantable member12 may be a cured implant shell, such as a conventional, relativelysmooth-surfaced, silicone-based elastomeric implant shell, for example,a shell intended to be filled with silicone gel or saline and used as abreast prosthesis.

A curable fluid composition 14, as described elsewhere herein, isapplied to the outer surface of the shell 12. FIG. 3 shows a partialcross sectional view of a shell 12 having a composition coating 10. Thismay be accomplished by dipping the shell (as shown by shaded line 13),while the shell is fixed to a mandrel (not shown) into a solution bathcontaining the curable fluid composition 14 (FIG. 1A). The composition14 comprises a silicone-based mixture including a solvent, and aleachable agent, as described elsewhere herein. The step of applying thecomposition 14 to the shell 12 may be accomplished by any suitable meansof application, such as dipping and spraying.

Next, the composition coating is allowed to stabilize on the shell 12.For example, the shell 12 can be held in a stable position until thecomposition coating no longer flows freely. This occurs as some of thesolvent evaporates from the coating, raising its viscosity. It can beappreciated that the step of allowing the composition to stabilize maybe accomplished by various means, for example, by allowing some of thesolvent to evaporate out of the composition or allowing a chemicalreaction to occur, inducing precipitation of the soluble components.Alternatively, stabilization can be achieved during crosslinking ofpolymerization of the silicone, or precipitation of the silicone orpore-forming material. Also, a combination of the above-mentionedmethods may be used for stabilization of the composition coating.

Once the composition 14 has stabilized on the shell 12, the second stepis to immerse (see shaded line 15) the shell 12 in a particle bath 16 toapply particles to the composition coating on the shell 12 (FIG. 1B).The particles 18 applied to a composition-coated shell 12 is depicted inFIG. 1B. FIG. 4 shows a partial cross sectional view of a shell 12 witha composition coat 10 and particles 18. Application of the particlecoating onto the shell 12, is performed while the composition coating onthe shell 12 is still tacky and able to retain the particles.Stabilizing the composition prior to particle application may beaccomplished by allowing at least some of the solvent in the compositionto evaporate out of the composition until the composition is stable andtacky but not fully cured. Another method, in accordance with one aspectof the invention, for stabilizing the composition is provided in theExample below.

Steps one and two can be repeated before the leaching step is carriedout, as indicated by shaded line 17. The steps of applying a curablefluid composition and applying a particle coating can be repeated, forexample, one or more times, for example, three, five or even up to 20times, until a final coating is applied. The final coating may be aparticle or a composition coating.

After the final coating of particles or fluid composition is applied tothe shell, the coated shell is then subjected to suitable curingconditions to solidify the composition with the particles embeddedtherein.

In the leaching step 19 (FIG. 1C), which takes place after thesolidification step described above, the embedded particles andleachable agent in the composition coating are immersed in a leachingbath 20 and removed. After the removal of the particles, what remains isa network of interconnected pores 21 (the structure may include bothrelatively large pores and relatively smaller pores, for example,micropores) on the shell.

Also see FIG. 7 for a flow chart of the process described herein.

Example 1

A mixture of about 7.5 wt. % PVA 2000 in water and about 40 wt. %acetoxy RTV silicone in xylene in a 3:1 volumetric ratio is prepared andhomogenized for 30 seconds. An acetyl mandrel is placed into the mixtureand coated uniformly as in a standard dip-coating process for themanufacturing of breast implant shells. The mandrel is then placed intoa fluidized bed reactor with salt granules until no more granules can bedeposited on the mandrel (about 5-10 seconds). This addition of saltparticles tends to dry and stabilize the mixture by absorbing some ofthe water, thereby increasing the viscosity of the mixture. The coatingis allowed to stabilize further at either 90° C. for about 15 minutes orat room temperature for about ½ hour, or otherwise sufficiently suchthat the next layer of composition may be applied. The procedure isrepeated 3-5 times to obtain a coating of desired thickness.

Final curing may be performed at 165° C. for 2 hours, leaching withwater or DCM for about 30 minutes for about 3 cycles with each (withagitation), and drying in vacuum overnight.

In one embodiment, a material is added to the composition before orafter the composition has been applied to the shell, the material beingeffective to increase the viscosity of the composition, for example, byabsorbing some of the solvent. When the leachable agent is in water, forexample, a salt can be added in order to dry/stabilize the phase byabsorbing the solvent. Other materials that may be helpful in thisregard include sugars and other appropriate materials that canaccelerate removal of solvent from the composition.

Next, a particle coating is applied to the composition to form the poresor cavities in the final elastomer foam structure. Application of theparticles may be accomplished by any suitable means, for example, bysprinkling and pressing the particles into the tacky compositioncoating, or by immersing the tacky, coated shell in a bath of theparticles. In the example shown, the particles are applied by immersingthe coated shell into a fluidized bath 18 comprising a fluidizationmedium 19, for example, air, and particulates, for example, saltparticles.

In some embodiments, the steps of applying the curable fluid compositionand applying the particle coating are then repeated one or more times,for example, from about 0.5 up to about 20 times, for example, about 1to about 10 times, for example, about 2 to about 5 times.

In one aspect of the invention, the particle coatings applied to thecomposition coatings may comprise coatings of particles havingrelatively different dimensions, one layer from the other. In otherwords, a first layer of particles may be relatively fine particles and asecond layer of particles may be relatively coarse particles, or viceversa.

It is contemplated that in some embodiments, interconnectivity betweenpores may be increased or controlled by causing the particulates in theparticle layer to fuse together. For example, in the event that theparticles are salt crystals, application of moist heat may be effectiveincrease interconnectivity thereof. Alternatively or additionally, anappropriate amount of a solvent for the particle material may be appliedin order to cause the particles to fuse together. Further informationwhich may be useful in appreciating this aspect of the invention may befound in copending, commonly owned U.S. Provisional Patent ApplicationNo. 61/177,955, filed on May 13, 2009 and entitled: IMPLANTS AND METHODSFOR MANUFACTURING SAME, the entire disclosure of which is incorporatedherein by this reference.

For example, in one embodiment, the steps of applying alternatingparticle and compositions coatings includes applying a first layer ofthe curable fluid composition to the shell, applying a first layer ofparticles, for example, relatively small particles, to the composition,applying a second layer of the composition to the first layer ofparticles, applying a second layer of particles, for example, relativelylarger particles, to the second layer of the composition. FIG. 5 is across sectional view of a shell showing alternating layers ofcompositions coatings 10 and particle coatings 18. In a specificembodiment, the first layer of particles comprises particles having anaverage size in a range of between about 30 microns to about 150microns, and the second layer of particles comprises particles having anaverage size in a range of between about 100 microns to about 450microns. In yet other embodiments, the method further includes applyinga third layer of the composition to the second layer of particles, andoptionally, providing a third layer of particles, to the third layer ofcomposition. The third layer of particles may have an average size in arange of between about 250 microns to about 750 microns.

The layered, coated shell is then subjected to suitable curingconditions to solidify and further stabilize the composition with theparticles embedded therein.

Next, the particles and leachable agent are then removed from the curedcoating, thereby revealing a network of highly interconnected poreswithin the cured elastomer. FIG. 6 shows the partial cross sectionalview of the shell 11 with a network of interconnected pores 21 after theremoval of the particles. The step of removing the particles maycomprise causing the particles to dissolve or contacting the particleswith an abrasive surface. In the same step or in a different step, theleachable agent in the composition layers are removed from theelastomer.

In some embodiments, a conventional gas foaming process is used inaddition to one or more of the presently described processes of theinvention. For example, prior to the steps of applying the compositionto the shell, the composition may be aerated by passing a gas, forexample, air, through the composition to aerate the composition andcreate bubbles therein. Advantageously, any surface skin that may beginto form on the aerated composition coating would be opened up duringextraction of the leachable phase to reveal highly interconnected poresresulting from the leachable materials, the particulates and the gasbubbles.

Removal of the particles and leachable agents may be accomplished byextracting these materials by exposing the layers to one or moresuitable mediums capable of dissolving the particles and/or leachableagents. For example, the coated shell is dipped or submerged in aleaching bath 19 (FIG. 1C). The leaching bath may comprise water or anaqueous solution containing an agent capable of dissolving, leaching orotherwise removing the leachable agent and/or particles while leavingthe cured elastomer substantially intact.

In some embodiments, the particles which are typically larger than thedispersed leachable agent, serve to create pores in the cured elastomerand the dispersed leachable agent serves to create micropores orinterconnections between the relatively larger pores.

The resulting open-cell structure is believed to facilitate tissueingrowth, improve fixation or adhesion of the implant and discouragesorganization of the collagen capsule which forms about the implant,which may help reduce capsular contraction.

In another aspect of the invention, an implantable composite member isprovided in which the composite member has an external surface at leasta portion of which is an open-cell porous structure, the compositemember being made by one of the processes described herein.

In yet other embodiments of the invention, each of the first and secondlayers of particles are made up of substantially uniformly sized/shapedparticles. In another aspect of the invention, each of the first andsecond layers of particles are made up of differently sized or shapedcomponents.

After finishing the shell according to the steps described above, thesteps required to make a finished mammary prosthesis may beconventional. First, any opening left by the mandrel support is patchedwith uncured silicone elastomer sheeting. If the prosthesis is to befilled with silicone gel, this gel is added and cured, the filledprosthesis packaged, and the packaged prosthesis sterilized. If theprosthesis is to be inflated with a saline solution, a valve isassembled and installed, the prosthesis is post cured if required, andthe prosthesis is then cleaned, packaged and sterilized. A combinationsilicone/saline mammary prosthesis can also be made.

A method has been described for creating an outer layer having anopen-cell structure in a silicone elastomer member. More specifically,the method can be applied to create a medical implant with an externalsurface layer of silicone elastomer having an open-cell structure, tocreate strips having a textured surface for control of scar formation,or to improve a process for making mammary prostheses. The product madeby this method has also been described and is expected to have greatutility in reducing capsular contraction, in preventing or controllingscar formation, and in anchoring medical implants.

Scar tissue formation in the healing of a wound or surgical incision isalso a process involving the growth of fibrous tissue. A visible scarresults from this healing process because the fibrous tissue is alignedin one direction. However, it is often aesthetically desirable toprevent scar formation, especially in certain types of plastic surgery.A member having an open-cell structure surface made in accordance withthe present invention can be placed subcutaneously within a healingwound or incision to prevent the fibrous tissue from aligning andthereby prevent or reduce scar formation.

It is often important to anchor medical implants against movement.Mammary prostheses are one example of implants that must be anchored.Facial implants are another example of implants that must be anchored.With facial implants it is particularly important that they be anchoredsecurely against movement because of their prominent location. Providingsuch implants with an open-cell structure surface made in accordancewith the present invention is a particularly advantageous way to ensurethat they will be anchored securely.

Example 2

A composition is prepared by mixing polyethylene glycol monomethyl ether(2000 Da), which will serve as a leachable agent, with a low viscositysilicone elastomer dispersion, for example, (e.g. polydimethylsiloxane,polydiphenylsiloxane, poly(dimethylsiloxane-co-diphenylsiloxane),poly(dimethylsiloxane-ran-diphenylsiloxane), etc.), in an organicsolvent (e.g. xylene), and at about 5 to about 40 wt %, or in somespecific embodiments, 17, 25 and 35 wt % of acetoxy RTV silicone. Thiscomposition is applied to the surface of an elastomeric shell held on amandrel or other mechanical support. The layer is allowed to evaporatemost of the solvent off.

A coating of sodium chloride crystals (about 250 μm to about 850 μmsize) are applied to the tacky composition layer by submerging thecoated shell into a fluidized bath of salt and air. This forms arelatively uniformly distributed single layer particle coating.

The elastomer is allowed to evaporate the solvent off and subsequentlycured at approximately 145° C.

The coated shell is then submerged in an aqueous washing medium atapproximately 40° C. and gently agitated to remove the particles andleachable agent.

Example 3

The same process is performed as in Example, 1, except that thecomposition is a mixture of 10 mL xylene, 10 mL DCM, 5 mL by dry volumePEG 2000 and 5 mL by dry volume acetoxy RTV silicone elastomer.

Example 4

The same process is performed as in Example 2, except that thecomposition is a mixture of

  5 mL water   1 mL xylene 0.5 mL by dry volume PVA 1500 0.2 mL by dryvolume RTV.

In another aspect of the invention, an article, for example a thin,flexible sheet, useful as a laminate, is provided. More specifically,the present invention provides a biocompatible sheet suitable for use asa laminate on an implantable device or object, in order to enhancetissue adhesion or ingrowth when the implantable device or object isimplanted in a patient. Thus, the manufacture of the materials inaccordance with the invention is not limited to conventional dippingprocesses but may be made by other suitable means, for example, throughthe lamination of a sheet that is prepared by molding or casting. Forexample, it is contemplated by the inventors that a sheet or laminatecan be prepared by casting the fluid material with all the componentspresent in various ratios (DCM, PEG)+(Xylene, RTV), and in someinstances, mixed and shaken with the particulate component, for example,salt crystals added to the liquid. The particulate and fluid mixture canbe shaken or mixed and cast onto a substrate or into a mold cavity. Insome embodiments, the particulate component comprises salt in a range ofabout 10% to about 99% of total dissolved solids. In a more specificembodiment, the salt is present at about 25% to about 60%. It can beappreciated that different amounts and different particle sizes/shapesof salt will produce laminates having different porosities. Once cured,the laminate can be laminated, by any conventional means known in theart, onto a medical device or implant or other object to be implanted ina body, for example, any object or device which would be improved by theaddition of such a laminate on one or more surfaces of the object ordevice. For example, the sheet may be laminated to catheter cuffs forlong term implantable catheters, dura-matter substitutes or the like.

Example 5

A laminate for an implant is prepared as follows. A fluid compositionmade up of 10 mL xylene, 10 mL DCM, 5 mL by dry volume PEG 2000 and 5 mLby dry volume acetoxy RTV silicone elastomer is mixed with 3.5 mL byvolume salt particles. This mixture is shaken together to ensuresubstantially uniform distribution of particles. The mixture is castmolded by applying the mixture to a mold surface to form a layer havinga uniform thickness of between about 1 mm to about 5 mm. The layer isallowed stabilize and is cured at about 120° C. for a sufficient periodof time. The cured sheet is removed from the mold surface and is thencontacted with a gentle spray of pure water to remove all of theleachable components and salt particles. The resulting, thin, flexible,porous silicone foam sheet is then further processed and sterilized andpackaged for sale or storage for later use as a laminate on a surface ofan implantable device.

Example 6

The process of Example 5 is performed with the additional steps ofrepeating, three times, the step of applying a fluidcomposition/particulate mixture to the stabilized layer prior to thestep of curing. The final thin, flexible sheet is a multilayered sheetand, in this example, has a thickness of greater than about 5 mm.

Example 7

The process of Example 5 is performed, however the cured stabilizedsheet is not contacted with a spray of water to remove the leachableagents and particulates before being packaged for sale or storage.Instructions are provided with regard to: removing the leachable agentsand particulates, sterilization, and bonding the sheet to a surface of amedical device.

Example 8

The process of Example 5 is performed to make two square sheets ofuncured foam, approximately 240 mm×240 mm. A layer of silicone adhesivein DCM is applied, by spraying or brushing, to one side of each of thesheets. The sheets are stretched uniformly and positioned one on top ofthe other, adhesive side facing each other, over a newly molded breastimplant shell filled with silicone or air. The foam sheets are joinedtogether at the edge of the implant and affixed by suitable clamps atthe perimeter of the implant. Twenty four hours later, the clamps areremoved. Excess foam is die-cut away from the implant by a press. Theimplant/foam is exposed to 140° C. for 2.5 hours for final post-curing.

While this invention has been described with respect to various specificexamples and embodiments, it is to be understood that the invention isnot limited thereto and that it can be variously practiced within thescope of the invention.

What is claimed is:
 1. A method of making a shell of an implantablebreast prosthesis having a textured surface, the method comprising thesteps of: (a) providing an implantable shell; (b) applying a curablefluid composition to the shell, the composition comprising a mixturecontaining an elastomer component, a leachable agent in the form ofdroplets in the mixture, and a solvent component; (c) applying a layerof particles to the composition; (d) allowing the composition tostabilize; and (e) removing the particles and the leachable agent fromthe stabilized composition, to form a composite material having anexternal surface at least a portion of which is an open-cell porousstructure defined by relatively large pores left by the removedparticles and relatively smaller pores, forming connections between therelatively large pores, left by the removed leachable agent.
 2. Themethod of claim 1 wherein the leachable agent is a water solublepolymer.
 3. The method of claim 1 wherein the leachable agent is anagent selected from the group of agents consisting of polyvinyl alcohol,polyethylene glycol, polyacrylic acid, polymethacrylate, poly-lactide,polyglycolide, polycaprolactone, polydioxanone, derivatives thereof,blends thereof, copolymers thereof, terpolymers thereof, andcombinations thereof.
 4. The method of claim 1 wherein the solventcomponent includes a solvent selected from the group consisting ofxylene, pentane, hexane, dichloromethane (DCM), dimethyl sulfoxide,dioxane, NMP, DMAc, and combinations thereof.
 5. The method of claim 1wherein the mixture is an emulsion.
 6. The method of claim 1 wherein theparticles comprise a material selected from the group of materialsconsisting of sodium chloride, barium sulfate, potassium nitrate, sodiumcarbonate.
 7. The method of claim 1 wherein the particles aresubstantially round.
 8. The method of claim 1 wherein the leachableagent is in the form of droplets having diameters in a range of betweenabout 50 microns to about 400 microns.
 9. The method of claim 1 whereinthe particles have an average particle size in a range of between about100 microns to about 900 microns.
 10. The method of claim 1 wherein theparticles have an average particle size in a range of between about 100microns to about 900 microns.
 11. The method of claim 1 furthercomprising the step of repeating steps (b) and (c) prior to the step ofremoving, to form a layered structure.
 12. The method of claim 1 whereinthe step of removing comprises contacting the stabilized compositionwith a solvent for the particles and the leachable agent.
 13. The methodof claim 1 wherein the leachable agent is in the form of droplets in themixture and the particles are angular in shape such that the porousstructure is defined by relatively large angular pores left by theremoved particles and relatively smaller pores, forming connectionsbetween the relatively large angular pores, left by the removeddroplets.
 14. A method of making a breast implant shell having anexternal surface at least a portion of which is an open-cell porousstructure, the method comprising the steps of: (a) providing animplantable shell; (b) applying a first layer of a curable fluidcomposition to the shell, the composition comprising a mixturecontaining an elastomer component, a leachable agent and a solventcomponent; (c) applying a first layer of particles to the composition;(d) applying a second layer of the composition to the first layer ofparticles; (e) applying a second layer of particles to the second layerof the composition; (f) allowing the composition to stabilize; and (g)removing the particles and the leachable agent from the stabilizedcomposition to form a composite material having an external surface atleast a portion of which is an open-cell porous structure defined byrelatively large pores left by the removed particles and relativelysmaller pores, forming connections between the relatively large pores,left by the removed leachable agent.